The following paragraphs are provided by way of background to the present disclosure. They are not however an admission that anything discussed therein is prior art or part of the knowledge of persons skilled in the art.
Alkaloids belonging to the class of chemical compounds known as morphinans (i.e. alkaloid morphinans) have long been recognized to be useful as therapeutic agents, and as precursor compounds for use in the manufacture of therapeutic agents. Neopine, for example, is produced by plants belonging to the Papaveraceae and has been isolated from opium poppy (Papaver somniferum) (Dobbie J. J. and Lauder, A. (1911), J. Chemical Society, 34-5). It is known that neopine in planta is produced from a precursor compound named thebaine. However it is not clear which plant genes and polypeptides are involved in catalyzing the conversion reaction(s) resulting in the production of neopine. Currently neopine may be harvested from natural sources, such as opium poppy. Alternatively, neopine may be prepared synthetically. The latter may be achieved by oxymercuration of thebaine or by reduction of or 14-bromocodeinone or 14-bromo-codeine (NaBH4) which yields neopine and its isomers (Poppy, the genus Papaver, 1998, pp 116, Harwood Academic Publishers, Editor: Bernath, J.)
The existing manufacturing methods for neopine and related morphinans however suffer from low yields of neopine and morphinans and/or are expensive. No methods exist to biosynthetically make neopine. There exists therefore in the art a need for improved methods for the synthesis of neopine and related morphinans.